1. Field of the Invention
The present invention relates generally to the cosmetic use of neurotoxin agents and more particularly to an improved method for injecting botulinum toxin (BTX).
2. Description of the Related Art
The position and appearance of the eyebrows is determined at rest and dynamically by the opposing action of several groups of muscles that act on the eyebrow. The frontalis muscle primarily performs eyebrow elevation. Brow elevation is opposed by the septal and orbital portions of the orbicularis oculi muscle, including the depressor supercilii component of the orbicularis oculi muscle, and the procerus muscle (D. Knize (1996) An anatomically based study of the mechanisms of eyebrow ptosis; Plast. Reconstr. Surg. 97:1321-33). The medial position of the eyebrow is also determined by the activity of the corrugator supercilii muscle. Additionally the shape of the brows is also determined by the activities of the eyebrow elevators and the eyebrow depressor muscles where they interdigitate along the eyebrow to create facial expression (A. Karacalar, et al (2005) Compensatory brow asymmetry: anatomic study and clinical experience; Aesthetic Plast. Surg 29: 119-23).
An aesthetically pleasing appearance is associated with relatively few lines in the forehead, no creasing between the eyebrows at the root of the nose, commonly known as the worry line, no lines across the bridge of the nose, and an absence of facial lines lateral to the eyes, commonly known as crow's feet. Additionally, with age there is a gradual fall in the position of the eyebrows creating hooding over the upper eyelids, which is known as brow ptosis. Aesthetically this change makes the eyes look small and is not desirable. Hooding of the upper eyelids by the descending eyebrow tissue results in a neural reflex that increases the activity of the frontalis muscle in an effort to keep the vision clear of the descending tissue that would otherwise obstruct vision or interfere with eyelid function (S. Teske, et. al. (1998) Hering's law and eyebrow position; Ophthal. Plast. Reconstr. Surg. 14: 105-6).
Botulinum toxin (BTX), which is produced by the bacterium Clostridium botulinum, inhibits the release of acetylcholine at the neuromuscular junction weakening muscle contraction. The degree of muscle paralysis will vary with the intensity of neuromusclular blockade. Several immunologically distinct botulinum toxin serotypes have been identified including A, B, C, D, E, F, and G. They vary in the severity and duration of the neuromuscular blockade and, consequently, the severity of the paralysis they produce (J. Melling, et. al. (1988) Clostridium botulinum toxins: nature and preparation for clinical use; Eye 2: 16-23). The term BTX is the generic term for this family of neurotoxins. Botulinum toxin A (BTX-A) is currently available from two commercial sources: Allergan Inc., Irvine, California, under the trade name BOTOX®, and from Ipsen Ltd., Slough, UK under the trade names DYSPORT® and RELOXIN®. Botulinum toxin B (BTX-B) is available from Solstice Neurosciences, Inc, South San Francisco, Calif., under the trade name MYOBLOC®. The relative strengths of these products vary. For purposes of clarity, dose and dilutions in the following discussions will refer to the widely available botulinum toxin A product by Allergan Inc. (BOTOX®). The dose and dilution must be adjusted for the other commercially available botulinum products according to their relative strength.
The first clinical application of botulinum toxin was by Dr. Allan Scott for the treatment of strabismus and then for a form of localized eyelid dystonia known as blepharospasm (A. Scott, et. al. (1973) Pharmacologic weakening of extraocular muscles; Invest Ophthalmol. 12:924-7). These were the first clinical applications approved by the FDA for treatment with botulinum toxin A (P. Savino and M. Maus (1991) Botulinum toxin therapy; Neurol. Clin. 9:205-24). Clinical use of botulinum toxin A in the treatment of spastic facial disorders lead to the clinical observation that many of the treated patients had improvement in the deep glabellar furrows between the eyebrows (J. Carruthers and A. Carruthers (1992) Treatment of glabellar frown lines with C. botulinum-A exotoxin; J. Dermatol. Surg. Oncol. 18:17-21). Recently, FDA approval was granted for the cosmetic use of botulinum toxin A for the treatment of the worry line between the eyebrows. Other FDA indications for botulinum toxin A include treatment for cervical dystonia, a type of neck spasm, and axillary hyperhydrosis, also known as excessive armpit sweating (R. Bhidayasiri and D. Truong (2005) Expanding use of botulinum toxin; J. Neurol. Sci. 235:1-9).
Botulinum toxin A is clinically used more broadly than what is approved by the FDA. This wider usage is permissible for licensed physicians and is referred to as “off label” use (J. Carruthers and A. Carruthers (2004) Botox: beyond wrinkles; Clin. Dermatol. 22:89-93). Cosmetically, BTX is used to soften dimpling in the chin, relax the depressor anguli oris muscle that contributes to a turned down corners of the mouth as detailed by Carruthers in U.S. Pat. No. 6,358,917, and a range of locations and effects around the eyes and in the forehead. Previously, BTX has been used to elevate the eyebrow position by treating between the eyebrows and at the lateral eyebrow with relatively few injection sites (24) and with relatively large quantities of BTX (1.5-2.5 Units Botulinum toxin A) (W. Huang, et. al. (2000) Browlift with botulinum toxin; Dermatol. Surg. 26:55-60). This technique is limited by fear of inducing the undesired side effect of ptosis of the upper eyelid, where the upper eyelid droops causing visual obstruction. This can be caused by the unwanted diffusion of BTX into the eyelid affecting the levator palpebrae superioris muscle responsible for eyelid elevation (A. Trindade De Alemeida and S. Cernea (2001) Regarding browlift with botulinum toxin; Dermatol. Surg. 27:848-849).
As will be disclosed below, the present inventor has found that it is possible to treat the eyebrow depressors extensively yet avoid the unwanted side effects by using a microdroplet injection technique and trapping the injected BTX between the skin and the orbicularis oculi muscle, the most important eyebrow depressor.